A method to co-encapsulate gas and drugs in liposomes for ultrasound-controlled drug delivery
A method to co-encapsulate gas and drugs in liposomes for ultrasound-controlled drug delivery
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DOI：
10.1016/j.ultrasmedbio.2008.01.005
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发表时间：
2008-08-01
影响因子：
2.9
通讯作者：
MacDonald, Robert C.
中科院分区：
文献类型：
--
作者：
Huang, Shao-Ling;McPherson, David B.;MacDonald, Robert C.
我们描述了一种新的方法，用于简便地生产含气体的脂质体，同时进行药物包封。磷脂和胆固醇的脂质体通过常规的方法制备的脂质膜的水化，超声，冷冻和解冻。该程序的一个单一但关键的修改产生含有气体（空气，全氟化碳，氩气）的脂质体;超声处理后，脂质与感兴趣的气体一起置于压力下。平衡后，将样品冷冻。然后将压力降低至大气压，并将悬浮液解冻。该程序导致中等（10 mg/mL）脂质浓度的脂质分散体中夹带高达10%体积的空气。包封的气体的量随着气体压力和脂质浓度而增加。使用0.32 mol/L甘露醇提供具有生理渗透压的水相，对4 mg脂质施加1、3、6或9 atm的压力。这导致在总共400 μ l脂质体分散体（10 mg脂质/mL）中分别包封10、15、20和30 μ l气体。气体包封的机制可能取决于空气（主要是氮气和氧气），像大多数溶质一样，在冰中溶解不良，并被排除在冷冻过程中形成的冰之外。然后，排除的空气作为气穴从溶液中出来，气穴通过脂质涂层以某种形式稳定。这些制剂中空气的存在使它们对超声波（1 MHz，8 W/cm（2），10 s）敏感，使得它们的含水含量（可能是水溶性药物）的多达一半可以通过短（10 s）的超声波应用而释放。该方法的诊断和治疗应用都是可以想到的。
We describe a novel method for the facile production of gas-containing liposomes with simultaneous drug encapsulation. Liposomes of phospholipid and cholesterol were prepared by conventional procedures of hydrating the lipid film, sonicating, freezing and thawing. A single but critical modification of this procedure generates liposomes that contain gas (air, perfluorocarbon, argon); after sonication, the lipid is placed under pressure with the gas of interest. After equilibration, the sample is frozen. The pressure is then reduced to atmospheric and the suspension thawed. This procedure leads to entrapment of air in amounts up to 10% by volume in lipid dispersions at moderate (10 mg/mL) concentrations of lipids. The amount of gas encapsulated increases with gas pressure and lipid concentration. Using 0.32 mol/L mannitol to provide an aqueous phase with physiological osmolarity, 1, 3, 6 or 9 atm of pressure was applied to 4 mg of lipid. This led to encapsulation of 10, 15, 20 and 30 mu l of gas in a total of 400 mu l of liposome dispersion (10 mg lipids/mL), respectively. The mechanism for gas encapsulation presumably depends on the fact that air (predominantly nitrogen and oxygen), like most solutes, dissolves poorly in ice and is excluded from the ice that forms during freezing. The excluded air then comes out of solution as air pockets that are stabilized in some form by a lipid coating. The presence of air in these preparations sensitizes them to ultrasound (1MHz, 8 W/cm(2),10 s) such that up to half of their aqueous contents (which could be a water soluble drug) can be released by short (10 s) applications of ultrasound. Both diagnostic and therapeutic applications of the method are conceivable.